TY - JOUR
T1 - Methods for assessment of the rate of onset and offset of insulin action during nonsteady state in humans
AU - Butler, P. C.
AU - Caumo, A.
AU - Zerman, A.
AU - O'Brien, P. C.
AU - Cobelli, C.
AU - Rizza, R. A.
PY - 1993
Y1 - 1993
N2 - Measurement of glucose turnover under non-steady-state conditions has proven problematic. When the mass of the glucose pool is not changing (i.e., glucose concentrations are constant) non-steady-state error can be minimized if all glucose entering the circulation has the same specific activity as plasma [radioactive infused glucose (hot-GINF) method]. Alternatively, a second tracer can be used to measure the effective volume of glucose [variable-pV method of Issekutz (T. Issekutz, R. Issekutz, and D. Elahi. (Can. J. Physiol. 52: 215-224, 1974)]. To determine whether these techniques provide concordant assessments of insulin action under non-steady-state conditions, glucose turnover was measured in six subjects. After initiation of insulin (0.6 mU · kg-1 · min-1), both methods indicated similar rates of suppression of hepatic glucose release, which was complete by ~100- 120 min. In contrast, the traditional fixed-pV method of Steele (R. Steele, J. Wall, R. DeBodo, and N. Altszuler. Am. J. Physiol. 187: 15-24 1956) underestimated turnover (P < 0.01) resulting in apparent complete suppression of glucose release within ~40 min (P < 0.01 vs. other methods). The hot- GINF and variable-pV methods also yielded similar estimates of turnover after discontinuation of insulin. Both indicated that resumption of hepatic glucose release was slower (P < 0.01) and fall of glucose uptake faster (P < 0.01) than suggested by the fixed-pV method. Thus both the hot-GINF and variable- pV methods avoid non-steady-state error introduced by the fixed-pV method and provide concordant assessments of the rate of onset and offset of insulin action.
AB - Measurement of glucose turnover under non-steady-state conditions has proven problematic. When the mass of the glucose pool is not changing (i.e., glucose concentrations are constant) non-steady-state error can be minimized if all glucose entering the circulation has the same specific activity as plasma [radioactive infused glucose (hot-GINF) method]. Alternatively, a second tracer can be used to measure the effective volume of glucose [variable-pV method of Issekutz (T. Issekutz, R. Issekutz, and D. Elahi. (Can. J. Physiol. 52: 215-224, 1974)]. To determine whether these techniques provide concordant assessments of insulin action under non-steady-state conditions, glucose turnover was measured in six subjects. After initiation of insulin (0.6 mU · kg-1 · min-1), both methods indicated similar rates of suppression of hepatic glucose release, which was complete by ~100- 120 min. In contrast, the traditional fixed-pV method of Steele (R. Steele, J. Wall, R. DeBodo, and N. Altszuler. Am. J. Physiol. 187: 15-24 1956) underestimated turnover (P < 0.01) resulting in apparent complete suppression of glucose release within ~40 min (P < 0.01 vs. other methods). The hot- GINF and variable-pV methods also yielded similar estimates of turnover after discontinuation of insulin. Both indicated that resumption of hepatic glucose release was slower (P < 0.01) and fall of glucose uptake faster (P < 0.01) than suggested by the fixed-pV method. Thus both the hot-GINF and variable- pV methods avoid non-steady-state error introduced by the fixed-pV method and provide concordant assessments of the rate of onset and offset of insulin action.
KW - activation
KW - deactivation
KW - glucose turnover
KW - hepatic glucose release
KW - non-steady-state error
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U2 - 10.1152/ajpendo.1993.264.4.e548
DO - 10.1152/ajpendo.1993.264.4.e548
M3 - Article
C2 - 8476033
AN - SCOPUS:0027417084
SN - 0002-9513
VL - 264
SP - E548-E560
JO - American Journal of Physiology - Endocrinology and Metabolism
JF - American Journal of Physiology - Endocrinology and Metabolism
IS - 4 27-4
ER -